“Get Smart About Antibiotics” An Introduction to Prudent Antibiotic Use

“Get Smart About Antibiotics”An Introduction to Prudent Antibiotic Use

Antibiotic Stewardship Curriculum

Developed by:Vera P. Luther, M.D.

Christopher A. Ohl, M.D.Wake Forest School of Medicine

With Support from the Centers for Disease Control and Prevention

Objectives1. Discuss untoward effects of antibiotic use2. Define antibiotic stewardship3. Describe 6 goals of antibiotic stewardship

programs4. Describe a rationale for antibiotic selection5. Describe directed and empiric antibiotic

therapy6. Describe and give examples of 4 tenets of

appropriate antibiotic use

Outline• Introduction• Untoward Effects of Antibiotics• Antibiotic Stewardship• Principles of Antibiotic Selection• Tenets of Appropriate Antibiotic Use• Conclusion

Introduction• The modern age of antibiotic therapeutics was

launched in the 1930s with sulfonamides and the 1940s with penicillin

• Since then, many antibiotic drugs have been developed, most aimed at the treatment of bacterial infections

• These drugs have played an important role in the dramatic decrease in morbidity and mortality due to infectious diseases

• While the absolute number of antibiotic drugs is large, there are few unique antibiotic targets

Untoward Effects of Antibiotics• Antibiotic resistance• Adverse drug events (ADEs)

– Hypersensitivity/allergy– Drug side effects– Clostridium difficile infection– Antibiotic associated diarrhea/colitis

• Increased health-care costs

Ohl CA, Luther VP. J. Hosp. Med. 2011;6:S4

Clostridium difficile Infection (CDI)

A potentially deadly colitis• Antibiotics are the

single most important risk factor for CDI

• Incidence and mortality increasing

• A more virulent NAP1/BI strain also seen with increasing frequency

Redelings, et al. EID, 2007;13:1417CDC. Get Smart for health care. Access at www.cdc.gov/Getsmart/healthcare

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Association Between Antibiotic Use and NonsusceptiblePneumococcal Infection

% S. pneumoniae who had recent antibiotic use

Study InfectionNonsusceptib

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p-value

Jackson

Invasive 56% 14% 9.3 0.009

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Invasive 65% 17% 9.3 <0.001

Tan Invasive 70% 39% 3.7 0.02

Nava Invasive 30% 11% 3.5 <0.001

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Bacteremia

57% 4% 3.6 <0.001

Block Otitis media

69% 25% 6.7 <0.001Dowell & Schwartz, Am Fam Physician. 1997 55(5):1647

Fluoroquinolone Use and Resistance among Gram-Negative

Isolates, 1993-2000

National ICU Surveillance Study

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Neuhauser, et al. JAMA 2003; 289:885

Limited Number of New Antibiotics to Combat Antibiotic

ResistanceNew Systemic Antibiotics Approved by the

FDA

Clin Infect Dis. 2011;52:S397-S428

Frequency of ADEs due to Antibiotics in Outpatient

Setting• 142,505 estimated emergency department

visits/year due to untoward effects of antibiotics– Antibiotics account for 19.3% of drug related adverse

events• 78.7% for allergic events• 19.2% for adverse events (e.g. diarrhea, vomiting)

– Approximately 50% due to penicillin & cephalosporin classes

– 6.1% required hospital admission

2004-2005 NEISS-CADES project

Shehab N et al. Clin Infect Dis. 2008;47:735

Consequences of Hospital Antibiotic Use

• At one tertiary care center 70% of Medicare patients received an antibiotic in 2010

• Approximately 50% of this use was unnecessary or inappropriate

• Untoward consequences of antibiotic therapy identified in this and other studies:– Inadequate treatment of

infection– Increased hospital readmissions– ADEs Polk et al. In: PPID, 7th ed.

2010Luther, Ohl. IDSA Abstract 2011

Antibiotic Stewardship• Definition: A system of informatics, data

collection, personnel, and policy/procedures which promotes the optimal selection, dosing, and duration of therapy for antimicrobial agents throughout the course of their use

• Purpose: – Limit inappropriate and excessive antibiotic

use – Improve and optimize therapy and clinical

outcomes for the individual infected patient Ohl CA. Seminar Infect Control 2001;1:210-21.Ohl CA, Luther VP. J. Hosp. Med. 2011;6:S4Dellit TH, et. al. Clin Infect Dis. 2007;44:159-177

• Is pertinent to inpatient, outpatient, and long-term care settings

• Is practiced at the– Level of the patient– Level of a health-care facility or system, or network

• Should be a core function of the medical staff (i.e. doctors and other healthcare providers)

• Utilizes the expertise and experience of clinical pharmacists, microbiologists, infection control practitioners and information technologists

Antibiotic Stewardship

Six Goals of Antibiotic Stewardship Programs

1. Reduce antibiotic consumption and inappropriate use

2. Reduce Clostridium difficile infections3. Improve patient outcomes4. Increase adherence/utilization of treatment

guidelines5. Reduce adverse drug events6. Decrease or limit antibiotic resistance

– Hardest to show– Best data for health-care associated gram negative

organismsTamma PD, Cosgrove SE. Infect Dis Clin North Am. 2011 25:245

Ohl CA, Luther VP. J. Hosp. Med. 2011;6:S4

Antibiotic Stewardship Improves Clinical Outcomes

RR 2.8 (2.1-3.8) RR 1.7 (1.3-2.1) RR 0.2 (0.1-0.4)

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AMP = Antibiotic Management ProgramUP = Usual PracticeFishman N. Am J Med

2006;119:S53.

Rates of C. difficile AADRates of Resistant

Enterobacteriaceae

Carling P et al. Infect Control Hosp Epidemiol. 2003;24(9):699-706.

Antibiotic Stewardship Reduces C. difficile Infection and Gram

Negative Resistance

Nine Factors to Consider When Selecting an Antibiotic

1. Spectrum of coverage2. Patterns of resistance3. Evidence or track record for the specified infection4. Achievable serum, tissue, or body fluid

concentration (e.g. cerebrospinal fluid, urine)5. Allergy6. Toxicity7. Formulation (IV vs. PO); if PO assess

bioavailability8. Adherence/convenience (e.g. 2x/day vs. 6x/day)9. Cost

Principles of Antibiotic Therapy

Directed Therapy (15%)• Infection well defined• Narrow spectrum• One, seldom two

drugs• Evidence usually

stronger• Less adverse reactions• Less expensive

Empiric Therapy (85%)• Infection not well defined

(“best guess”)• Broad spectrum• Multiple drugs• Evidence usually only 2

randomized controlled trials

• More adverse reactions• More expensive

Why So Much Empiric Therapy?

• Need for prompt therapy with certain infections– Life or limb threatening infection– Mortality increases with delay in these cases

• Cultures difficult to do to provide microbiologic definition (i.e. pneumonia, sinusitis, cellulitis)

• Negative cultures• Provider Beliefs

– Fear of error or missing something– Not believing culture data available– “Patient is really sick, they should have ‘more’ antibiotics”– Myth of “double coverage” for gram-negatives e.g.

pseudomonas– “They got better on drug X, Y, and Z so I will just continue those”

To Increase Directed Therapy for Inpatients:

• Define the infection 3 ways – Anatomically, microbiologically, pathophysiologically

• Obtain cultures before starting antibiotics• Use imaging, rapid diagnostics and special

procedures early in the course of infection• Have the courage to make a diagnosis• Do not rely solely on “response to therapy” to guide

therapeutic decisions; follow recommended guidelines

• If empiric therapy is started, reassess at 48-72 hours– Move to directed therapy (de-escalation or streamlining)

To Increase use of Directed Therapy for Outpatients:

• Define the infection 3 ways – Anatomically, microbiologically, pathophysiologically

• Obtain cultures before starting antibiotics– Often difficult in outpatients (acute otitis media, sinusitis,

community-acquired pneumonia)

• Narrow therapy often with good supporting evidence– Amoxicillin or amoxicillin/clavulinate for AOM, sinusitis and

CAP– Penicillin for Group A Streptococcal pharyngitis– 1st generation cephalosporin or clindamycin for simple

cellulitis– Trimethoprim/sulfamethoxazole or cipro/levofloxacin for

cystitis

Tenet 1: Treat Bacterial Infection, not Colonization

• Many patients become colonized with potentially pathogenic bacteria but are not infected– Asymptomatic bacteriuria or foley catheter colonization– Tracheostomy colonization in chronic respiratory failure– Chronic wounds and decubiti– Lower extremity stasis ulcers– Chronic bronchitis

• Can be difficult to differentiate– Presence of WBCs not always indicative of infection– Fever may be due to another reason, not the positive

culture

Tenet 1: Treat Bacterial Infection, not ColonizationExample: Asymptomatic bacteriuria

• ≥105 colony forming units is often used as a diagnostic criteria for a positive urine culture

• It does NOT prove infection; it is just a number to state that the culture is unlikely due to contamination

• Pyuria also is not predictive on its own• It is the presence of symptoms AND

pyuria AND bacteruria that denotes infection

Prevalence of Asymptomatic Bacteriuria

Age (years) Women Men20 1% 1%70 20% 15%>70 + long-term care 50% 40%Spinal cord injury 50% 50%(with intermittent catheterization)

Chronic urinary catheter 100% 100%

Ileal loop conduit 100% 100%

Nicolle LE. Int J Antimicrob Agents. 2006 Aug;28 Suppl 1:S42-8.

Treatment of Asymptomatic Bacteriuria in the Elderly

Multiple prospective randomized clinical trials

have shown no benefit• No improvement in “mental status”• No difference in the number of

symptomatic UTIs• No improvement in chronic urinary

incontinence• No improvement in survival

Summary of Asymptomatic Bacteriuria Treatment

• Treat symptomatic patients with pyuria and bacteriuria• Don’t treat asymptomatic patients with pyuria and/or

bacteriuria• Define the symptomatic infection anatomically• Dysuria and frequency without fever equals cystitis• Dysuria and frequency with fever, flank pain, and/or

nausea and vomiting equals pyelonephritis• Remember prostatitis in the male with cystitis

symptoms

• CAP: often a difficult diagnosis• X-rays can be difficult to

interpret. Infiltrates may be due to non-infectious causes.

• Examples:–Atelectasis–Malignancy–Hemorrhage–Pulmonary edema

Tenet 2: Do not Treat Sterile Inflammation or Abnormal Imaging

Without InfectionExample: community-acquired pneumonia (CAP)

• Pneumonia is not present in up to 30% of patients treated

• Do not treat abnormal x-rays with antibiotics if the patient does not have systemic evidence of inflammation (fever, wbc, sputum production, etc)

• Discontinue antibiotics initially started for pneumonia if alternative diagnosis revealed

Community-Acquired Pneumonia (CAP)

• Acute bronchitis• Common colds• Sinusitis with symptoms

less than 7 days• Sinusitis not localized to

the maxillary sinuses• Pharyngitis not due to

Group A Streptococcus spp.

Gonzales R, et al. Annals of Intern Med 2001;134:479Gonzales R, et al. Annals of Intern Med 2001;134:400Gonzales R, et al. Annals of Intern Med 2001;134:521

Tenet 3: Do not Treat Viral Infections with Antibiotics

Tenet 4: Limit Duration of Antibiotic Therapy to the

Appropriate Length• Ventilator-associated pneumonia: 8 days• Most community-acquired pneumonia: 5 days• Cystitis: 3 days• Pyelonephritis: 7 days if fluoroquinolone used• Intra-abdominal with source control: 4-7 days• Cellulitis: 5-7 days

Hayashi Y, Paterson DL. Clin Infect Dis 2011; 52:1232

Other Tenets of Antibiotic Stewardship

• Re-evaluate, de-escalate or stop therapy at 48-72 hours based on diagnosis and microbiologic results

• Re-evaluate, de-escalate or stop therapy with transitions of care (e.g. ICU to step-down or ward)

• Do not give antibiotic with overlapping activity

• Do not “double-cover” gram-negative rods (i.e. Pseudomonas sp.) with 2 drugs with overlapping activity

• Limit duration of surgical prophylaxis to <24 hours perioperatively

• Use rapid diagnostics if available (e.g. respiratory viral PCR)

• Solicit expert opinion if needed• Prevent infection

– Use good hand hygiene and infection control practices

– Remove catheters

Other Tenets of Antibiotic Stewardship

Conclusion• The therapeutic benefit of antibiotics should be

balanced with their unintended adverse consequences

• Inappropriate antibiotic use is associated with increased antibiotic resistance, adverse drug effects and Clostridium difficile infection

• Antibiotic stewardship is important for preserving existing antibiotics and improving patient outcomes

• Antibiotic prescribing should be prudent, thoughtful and rational

“Get Smart About Antibiotics” An Introduction to Prudent Antibiotic Use

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